medwireNews: The interleukin (IL)-23 inhibitor risankizumab is an effective and well-tolerated treatment for moderate-to-severe active ulcerative colitis, show the results of two double-blind, placebo-controlled phase 3 studies.
In both the INSPIRE induction study and the COMMAND maintenance study, risankizumab enabled more people to reach the primary endpoint of clinical remission, which was determined using the adapted Mayo score (stool frequency ≤1 and not greater than the baseline score, rectal bleeding score 0, and endoscopic subscore ≤1 without friability), at 12 and 52 weeks, respectively.
Moreover, there were improved endoscopic and histologic findings, with no untoward effects beyond those already observed with the drug in its other indications of Crohn’s disease, plaque psoriasis, psoriatic arthritis, and palmoplantar pustulosis, Edouard Louis (University Hospital CHU of Liège, Belgium) and co-investigators report in JAMA.
“Further study is needed to identify benefits beyond the 52-week follow-up,” the INSPIRE and COMMAND Study Group authors conclude.
INSPIRE and COMMAND were two complementary studies, recruiting participants who had moderate-to-severe active disease and who had a history of intolerance or inadequate response to one or more conventional therapies, advanced therapies, or both, and who had not been previously exposed to risankizumab.
Participants in the INSPIRE induction study were randomly allocated to receive 1200 mg of risankizumab or placebo, which were given intravenously at weeks 0, 4, and 8. Of the 975 individuals whose data could be analyzed, clinical remission at 12 weeks was observed in a respective 20.3% of 650 and 6.2% of 325, a significant difference.
The COMMAND study included 548 people who had participated in INSPIRE and were randomly allocated to receive subcutaneous treatment every 8 weeks with risankizumab, at doses of 180 mg or 360 mg, or placebo. The clinical remission rates at week 52 were again significantly higher for risankizumab than placebo, at a respective 40.2% of 179, 37.6% of 186, and 25.1% of 183.
Safety outcomes for both the induction and maintenance trials were “consistent” with those previously reported for risankizumab in patients with Crohn’s disease, the researchers say. Serious adverse events in the INSPIRE trial occurred in 2.3% of risankizumab-treated patients versus 10.2% of controls, and the rates in the COMMAND trial were 5.2% for the 180 mg dose and 13.8% for the 360 mg dose of risankizumab versus 11.7% for placebo.
Gilaad Kaplan (University of Calgary, Alberta, Canada) writes in an accompanying editorial that the trial findings have led to marketing approval for risankizumab and as such it “adds to a growing list of biological drugs and oral small molecules that have proven efficacy in treating patients with moderate to severe ulcerative colitis.”
The challenge that gastroenterologists have now is which drug to use, and in what order, Kaplan says. Should risankizumab be used in people who are no longer responsive to ustekinumab which targets IL-23 and IL-12, he asks. And would risankizumab be a better choice for those who have not already been treated with ustekinumab?
“Some lessons may be learned from clinical studies in Crohn disease,” Kaplan suggests, where risankizumab has been shown to be noninferior to ustekinumab and associated with better responses when used in people who have not previously been exposed to ustekinumab. Prior use of ustekinumab was one of the main exclusion criteria in the INSPIRE and COMMAND studies.
“[H]ead-to-head trials are necessary in patients with ulcerative colitis as physicians, patients, and payers balance the potentially greater efficacy of newer IL-23 inhibitors against the lower cost of the biosimilar ustekinumab,” Kaplan concludes.
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JAMA 2024; doi:10.1001/jama.2024.12414
JAMA 2024; doi:10.1001/jama.2024.8819
